1. Field of the Invention
The present invention relates to apparatus for measuring the genetic sequence of biopolymers, such as DNA and protein.
2. Description of the Prior Art
The DNA chip for hybridization described in the published Japanese translation of patent application Ser. No. 512,605 of 1999 is configured in such a manner that a large number of electrodes are formed on a substrate and a current source is connected to each of these electrodes. There are 100 to 10,000 electrodes on the substrate and, in normal applications, a different type of DNA segment is fixed to each electrode.
By flowing unknown DNA segments onto the substrate to which known DNA segments are fixed for hybridization as described above, it is possible to have an unknown DNA segment combine with its corresponding DNA segment. If the unknown DNA segment is labeled with a fluorescent reagent, the sequence of the unknown DNA segment that has combined with any known DNA segment can be determined.
The prior art cited above will now be described in further detail. As shown in FIG. 1, a positive voltage is applied to an electrode 1 to which a known DNA segment indicated by 2 is fixed. Since DNA is negatively charged, an unknown DNA segment indicated by 3 is attracted toward the electrode 1 where the known DNA segment 2 is fixed, as shown in FIG. 1b. As a result, hybridization that used to take several hours to finish is completed in only several tens of seconds.
The combining force is weak in case known and unknown DNA segments with different sequences wrongly combine with each other, as shown in FIG. 2a. Thus means the segment pair can be separated by applying a weak negative voltage to the electrode 1 after hybridization, as shown in FIG. 2b. Thus, it is possible to precisely measure even a single-base difference as seen in such DNA samples as SNPs (single nucleotide polymorphisms).
Such a DNA chip as described above is housed in a cartridge together with, for example, a fluid system combined with a detection system.
This DNA chip has had the following problems, however:
1) Cartridges are designed to be disposable, as a rule. On the other hand, the prior art cartridge requires a large number of electrodes and electrical connection terminals to be formed thereon and, therefore, is costly. Furthermore, electrodes and their processing circuits are also required for a reading unit used with the cartridge. Thus, the cost of a total system also is high.2) Since the electrical connections of the DNA chip are made of electrodes, metal surfaces in contact with a solution are liable to cause electrochemical noise or fluctuations. Furthermore, electrical contact with the terminals of the reading unit tends to become defective.3) The DNA chip requires electrodes and their electrical taps to be formed on the cartridge, thereby increasing the size of the cartridge. The reading unit also requires such elements as terminals and voltage supply circuitry.